Body fluid collector and separator having improved flow rate

ABSTRACT

DIAGNOSTIC BODY FLUID COLLECTOR AND ANALYTICAL SAMPLE SEPARATOR INCLUDING AN EVACUATED BODY FLUID COLLECTING TUBE AND AN EVACUATED ANALYTICAL SAMPLE CUP. THE COLLECTING TUBE AND THE SAMPLE CUP ARE PHYSICALLY SEPARATED FROM EACH OTHER BY ONE OR MORE SELECTIVELY PERMEABLE BARRIERS   THROUGH WHICH ONLY A PORTION OF THE COLLECTED FLUID WILL PASS. THE ASSEMBLY ALSO INCLUDES A HOLLOW CONDUIT FOR DIRECTING BODY FLUIDS INTO THE BODY FLUID COLLECTING TUBE.

Aug. '8, 1972 E. W. STONE BODY FLUID COLLECTOR AND SEPARATOR HAVING IMPROVED FLOW RATE Filed July 31, 1970 3 Sheets-Sheet. 1

FIG. I

FIG. 2

INVENTOR ELLERY w. STONE MM Mm ATTORNEYS E. w. STONE 3,682,596

BODY FLUID COLLECTOR AND SEPARATOR HAVING IMPROVED FLOW RATE Aug. 8, 1972 3 Sheets-Sheet 2 Filed July 31, 1970 FIG. 3

MENTOR 'ELLERY W. STONE BY W ATTORNEKS 1972 E. w. STONE 3,6

BODY FLUID COLLECTOR AND SEPARATOR HAVING IMPROVED FLOW RATE Filed July 31, 1970 3 Sheets-Sheet S 1 3g 5 I I 6! 3o g 1' I \j 62 \,e5

I INVENTOR ELLERY W. STONE ATTORNEY United States Patent Office 3,682,596 Patented Aug. 8, 1972 3,682,596 BODY FLUID COLLECTOR AND SEPARATOR HAVING IMPROVED FLOW RATE Ellery W. Stone, Cohasset, Mass, assignor to Schering Corporation, Bloomfield, NJ.

Continuation-impart of application Ser. No. 677,196,

Oct. 23, 1967. This application July 31, 1970,

Ser. No. 60,044

Int. Cl. B01d 29/00; G01n 33/16 U.S. Cl. 23253 R Claims ABSTRACT OF THE DISCLOSURE This application is a continuation-in-part of my application Ser. No. 677,196, filed Oct. 23, 1967 and now US. Pat. No. 3,539,300, issued Nov. 10, 1970.

It is a principal object of the present invention to overcome a major drawback of existing automated or semiautomated tehniques for chemical, microbiological, hematological or other analyses of blood or other body fluids, all of which depend upon extensive and time-consuming manipulation of the body fluid for the purpose of separating it into the analytical sample or samples prior to presentation to an automated analytical machine or a skilled analyst. It is a further object of this invention to minimize the chances of error by providing a means for positive identification of the analytical sample with the patient from whom the body fluid was withdrawn.

To achieve the objects specified above and thereby relieve the shortage of skilled physicians and allied health personnel it is a further object of the present invention to provide a device for collecting a body fluid and automatically producing an analytical sample therefrom, which sample is formed without first removing the collected body fluid from the collector device and in general without manipulation by the collecting physician or allied health worker. A particularly useful application of the present invention is as a disposable device for collecting a portion of blood or other body fluid and automatically producing a sample of serum, plasma, protein free filtrate, or other fraction by automatic processing of the collected body fluid as it is being transported from the patient to the laboratory. Such automatic processing can include filtration, fluid flow through a selectively permeable barrier or barriers, and/or reaction with selected chemical reagents.

A second particularly useful application of the present invention is as a disposable device for collecting a portion of blood or other body fluid and automatically producing a concentrated sample of microorganisms for microbiological analysis and a separation of microorganisms of diflerent size such as bacteria, rickettsia, and viruses by automatic filtration of the collected body fluid through one or more selectively permeable membranes or porous separators for individual analysis.

It is a further object of the present invention to reduce the dangers of laboratory induced infection when dealing with potentially pathogenic body fluids by providing a self contained system for body fluid collection and analytical sample separation.

It is a further object of the present invention to provide a body fluid collector and analytical sample separation means which is extremely simple in construction, automatic in operation and relatively inexpensive to manufacture whereby the device may be discarded after a single use.

Another object of the present invention is to provide a releasable sample cup designed to be marked with a pencil or other writing instrument or label to directly identify the body fluid and the analytical sample with the patient at the time the body fluid is collected from the patient and to carry such positive identification directly to automatic analytical instrumentation where so applied, by being designed to fit the turntable or other sample container holder of such automatic analytical instrumentation.

These and other objects and advantages are provided by a body fluid collector and analytical sample separator device including an evacuated body fluid collecting tube, an especially designed evacuated analytical sample cup releasably secured to one end of the collecting tube, one or more sample separating, selectively permeable barriers forming a passage between the tube and cup, and means forming a conduit for directing a body fluid into the other end of the body fluid collecting tube.

The invention will be more particularly described in reference to the accompanying drawings wherein:

FIG. 1 is an assembled view of one version of the body fluid collector and analytical sample separator device of the invention;

FIG. 2 is an enlarged partial fragmentary exploded view of the structure shown in FIG. 1;

FIG. 3 is an enlarged view substantially on line 3-3 of FIG. 1;

FIG. 4 is a section on line 4-4 of FIG. 3;

FIG. 5 is an enlarged fragmentary sectional view of a modified form of closure means for a device of the type illustrated in FIG. 1; and

FIG. 6 is an enlarged partial fragmentary exploded view of another version of the body fluid collector and analytical sample separator provided with a series of selectively permeable barriers in such a manner that several diiferent analytical samples can be obtained.

Referring to the drawing 10 generally designates an improved diagnostic body fluid collector and sample separator. Beginning at the rear end of the device it includes an analytical sample cup 12, a porous support 16, a selectively permeable barrier disc 14, a collector tube 18, and a resilient stopper 20. This unit, when in use, is assembled with a barrel member 22, a double ended needle 24, and a needle holder 26. Each of the foregoing elements will be more particularly described hereinafter.

Referring particularly to FIG. 3 of the drawings, the sample collecting tube 18 consists of a generally cylindrical member having an internal flange 30 adjacent one of its ends. The tube 18 is preferably formed of a transparent or translucent plastic material and in the case of a blood collecting device the tube 18 would be approximately 4" long and have an internal diameter of about The upper or front end 32 of the tube 18 receives a conventional resilent rubber stopper 20 of the type adapted to be punctured by the inner sharpened end 34 of the double ended hollow needle 24.

The analytical sample receiving cup 12 is also cast or injection molded of plastic and its upper end, as viewed in FIG. 3, is provided with a flange 38. A portion 39 of the outer surface of the analytical sample cup 12 is provided with a roughened surface or other suitable surface for marking with a pencil or other writing instrument, or for application of a label to permit identification of the sample with the patient at the time the body fluid is collected. This identifying mark or marking can include a magnetic label or other designation capable of being interpreted by a computer or computer input device. The

external diameter of the upper end of the sample cup 12 is such that it is snugly receivable within the bore 40 in the collector tube 18 and the upper surface of the flange 38 is adapted to abut against the lower peripheral edge of the tube. The atmosphere inside the tube 18 and the cup 12 is maintained, prior to use, at an absolute pressure of from about 0.5 to about inches of mercury. The lower surface of the flange 38 and the outer diameter of the sample cup 12 below the flange are designed so that the cup can be inserted into a hole in a turntable or other sample container holder of automated analytical equipment, and will be retained by the flange 38. This portion of the assembly also includes, as hereinbefore described, a selectively permeable barrier disc 14 and a porous support disc 16. The upper surface, as viewed in FIG. 3, of the selectively permeable barrier disc 14 shoulders against the internal flange 30 and the peripheral edge of the porous support 16 also as viewed in FIG. 3, is fitted snugly against the bore 40 in the collector tube 18 whereby the porous support and the selectively permeable barrier disc are immovably maintained within the lower portion of the bore 40 in the sample receiving tube 18. The lower peripheral surface of the porous support disc 16 is seated against the upper edge of the cup 12.

The barrel member 22, as shown in 'FIGS. 1 and 2 of the drawing, is of generally conventional design and is of the type adapted to be used with vacuum blood sampling tubes. The lower end of the barrel member 22 is closed except for a threaded bore which receives the threads 44 on the needle retaining member 26. When the threads 44 of the member 26 are screwed into the end of the barrel portion 22 the double ended needle projects outwardly and inwardly generally as illustrated in FIG. 2 of the drawings. The internal diameter of the barrel member 22 is such that the outer cylindrical surface of the resilient rubber stopper member 20 snugly engages the inner surface, and once the barrel portion 22 is positioned such that the lower extended end 44 of the needle 24 is within a patients vein, telescopic movement of the sample collector tube 18 inwardly of the barrel portion 22 such that the inner portion 34 of the needle 24 pierces the resilient stopper 20, as illustrated in FIG. 3 of the drawings, blood is drawn from the patient into the sample collecting tube 18 by a vacuum produced within the tube during its manufacture and/ or assembly.

After the collecting tube 18 is filled with the desired quantity of blood from the patient, the tube may be removed from the barrel portion 22 and placed in a storage rack with the sample cup 12 pointing downwardly. At this stage the stopper 20 is removed from the end 32 of the tube 18 or is vented so that atmospheric pressure will assist in forcing a part of the collected blood through the filter or other selectively permeable barrier. When the device is used for microbiological applications the original stopper is replaced with a cotton plug or other protective closure to prevent contamination of the body fluid with additional microorganisms. During this process a portion of the blood such as serum, plasma or other analytical sample, will be drawn through the selectively permeable barrier 14 and the porous support 16 into the sample cup.

Atfer the analytical sample has collected in the sample cup 12, the sample cup 12 may be removed from the tube 18 at the telescopic connection between these two elements.

The type of selectively permeable barrier, or filter, that is employed in the collector is determined by the nature of the fluid being filtered and the type of filtrate desired. In general, there are two classes of filters which can be used advantageously in the diagnostic collection and separation of blood. The two general classes comprise:

(1) microporous membrane filters and,

(2) thin skin dilfusion membrane filters.

The first group, microporous membrane filters, are well known in commerce and have been used in many types of analytical chemistry procedures and for clarifying liquids,

purifying air supplies, and pasteurizing beer by the removal of yeast particles therefrom. Although a variety of polymers can be used to fabricate such filters, the majority of the commercial microporous membranes are made of cellulose derivatives, especially cellulose diacetate and triacetate. A wide range of pore size is commercially available and the pore size range of microporous membrane filters are generally from about 0.22 to about 10 microns.

-In addition to the polymer microporous membrane filters discussed above, microporous metal filters, sintered ceramic and sintered glass filters may also be employed in the device of the invention.

)In order to exclude blood cells from the serum or other sample, a microporous membrane filter must have a pore size small enough to retain cells approximately 5 to 8p in diameter and yet large enough to permit relatively rapid flow of the liquid analytical sample. Where blood plasma is to comprise the filtrate, a flow time for 3 mls. of sample in the neighborhood of about 20 minutes has been obtained with a microporous membrane filter disc of approximately /4" diameter.

In the alternative version of the device to be used to prepare samples for microbiological analysis, several microporous membrane filters are arranged in series as shown in FIG. 6 so that large malignant cells are retained by the first filter 61, erythrocytes, leukocytes and platelets are retained by the second filter 62, and bacteria are retained by the third filter 63. :If desired, rickettsia would be retained by a fourth filter and viruses by a fifth tfilter. A greater or lesser number of filters are used as appropriate for the application. The filters are held by flanged plastic cylinders 65 releasably secured to the body fluid connecting tube 18, the sample cup 12, and to each other such that each forms a sample chamber 'when removed from the assembly. These chambers are designed in such a way that the sample of microorganisms can be transferred directly to the appropriate culture medium for growth and analysis.

The thin skin diffusion membrane filter differs from microporus varieties in that the membrane filter has a thin, unbroken skin on one surface and graded porosity through the body of the filter material. Such membranes have been used for the reverse osmosis processes used for desalination of sea water and a number of methods of making such membranes have been described in the technical literature.

The thin sk-in diffusion membrane filters have advantages when used with the structure of the present invention as there are no pores on the surface of the skin which could become clogged by red cells or protein molecules. Furthermore thin skin diffusion membrane filters can be made with selective permeability based on the molecular weight and/or other physicochemical properties of the components of the body fluid sample. The thin skin diffusion membrane used in the device is appropriately selected to be permeable to the component or components of the body fluid which are sought in the analysis of the sample. For example, a thin skin diffusion membrane permeable to species with molecular weight less than 200,000 is used to separate fibrinogen and all other higher molecular weight constituents from blood for the preparation of sermum using the present device. In cases where it is desired to obtain several analytical samples each containing different sets of constituents then the form of the device illustrated in FIG. 6 is used with appropriately selected thin skin difiusion membrane filters. Another version of the device incorporates a series of selectively permeable barriers some of which are microporous membrane filters and some 'of which are thin skin diffusion membrane filters. [For example, a device designed to separate malignant cells, normal blood cells, and a protein free filtrate from blood, includes two selectively permeable barriers in series. The first such barrier is a microporous membrane filter with pore size of approximately 10 microns which retains malignant cells and transports other constituents. The second barrier is a thin skin diffusion membrane filter permeable to those constituents of blood with molecular weight less than approximately 10,000, which retains normal blood cells and proteins and transports electrolytes, glucose, urea, and other low molecular weight constituents.

It will also be appreciated by those skilled in the art that where higher flow rates are desired the disc shape filter 14 may be replaced by a dished, conical or cup shaped filter which would be maintained within the structure by, for example, the flange means illustrated in FIG. 3.

Referring for example to FIG. of the drawings, a modified form of stopper is illustrated, In FIG. 5 the stopper 50, which may be constructed of plastic, synthetic or natural rubber or the like, is provided with an opening 52 therethrough which opening is adapted to snugly receive a resilient elastomeric closure member 54. The closure member 54 has a thin cross web 56 through which the sharp end of the needle 24 may be readily pressed and, once the tube 18 is filled with blood, the entire resilient closure member 54 may then be removed as shown in broken lines at A, to vent the interior of the tube 18 to atmospheric pressure. It will also be noted that in the illustrated form of the stopper 50 the resilient closure member 54 is positioned oif center. The needle 24 in the needle holding barrel member 22 would also be positioned oif center and can thereby be inserted at an acute angle to, for example, the arm of the patient. A protrusion 57 on the rim of the stopper 50 opposite to the closure member 54 facilitates the alignment of the off center needle 24 with the off center closure member 54 by sliding in a groove provided in the barrel member 22.

From the foregoing description of a preferred and of a modified form of the body fluid collector and separator of the present invention, it will be seen that the objects and advantages hereinbefore set forth are fully accomplished. It will be appreciated that body fluid, the permeable barrier and the analytical sample may be selected for clinical chemical analysis; microbiological analysis; hematological analysis, or cytological analysis.

I claim:

1. A body fluid collector and analytical sample separator device including an evacuated body fluid collecting tube having a first end and an opposing second end, means sealingly closing said first end, an evacuated analytical sample cup having a closed end and an opposing end, said sample cup being releasably secured at it opposing end to the second end of the collecting tube, a sample separating, permeable barrier closing off the second end of the collecting tube and forming a strain flow passage between the interiors of the tube and the cup when the cup is secured to the tube, and means for directing a body fluid into the interior of the body fluid collecting tube through the first end thereof.

2. The invention defined in claim 1 wherein said sample-separating, permeable barrier comprises a microporous membrane.

3. The invention defined in claim 1 wherein said sample separating, permeable barrier comprises a thin skin diifusion membrane.

4. The invention defined in claim 1 wherein a series of said barriers are provided and are spaced apart lengthwise of the tube adjacent the second end thereof, said series of said barriers being comprised of both microporous membranes and thin skin diffusion membranes.

-5. The invention defined in claim 1 wherein said second end of the tube is provided with an internal flange and said sample cup is telescopically insertable at its open end in said second end of the tube and the separating permeable barrier is maintained between said internal flange and the end edge of the inserted end of the sample cup.

6. The invent-ion defined in claim 1 including a series of barriers spaced apart lengthwise of the tube and the cup and forming the passage between the tube and the cup.

7. The invention defined in claim 6 wherein said permeable barriers are releasably secured to the tube, the sample cup, and each other such that several analytical samples are separated from the collected body fluid.

8. A body fluid collector and analytical sample separator device including an evacuated body fluid collector tube having a first end and an opposing second end, a resilient stopper sealing fitted on and closing off the first end of the tube, an evacuated analytical sample cup having a closed end and an opposing end, said sample cup being releasably secured at its opposing end to the second end of the collecting tube, and a sample separating permeable barrier closing 01f the second end of the tube and forming a strain flow separation passage between the interior of the tube and the interior of the cup when the cup is secured to the tube, said sealing stopper being formed so as to be pierced by a hollow needle for directing a body fluid into the body fluid collecting tube through the first end thereof.

References Cited UNITED STATES PATENTS 3,200,813 8/1965 Christakis 128-2 F 3,300,051 1/1967 Mitchell 210-339 3,448,041 6/1969 Swank 210'-335 X MORRIS O. WOLK, Primary Examiner R. M. REESE, Assistant Examiner US. Cl. X.'R.' 

